Device And Method For Delivering Or Withdrawing A Substance Through The Skin

ABSTRACT

An apparatus for delivering or withdrawing a fluid through at least one layer of the skin is provided. A device includes a body having a top face, a bottom face, a side edge and at least one channel. The bottom face includes a first surface area and a second surface area adjacent to and recessed at a first distance from the first surface area. The bottom face further includes at least one raised protrusion disposed on the second surface area. The protrusion has a height from the first surface greater than the first distance. At least one dermal-access member is provided in the protrusion and is in fluid communication with the channel to deliver or withdraw the fluid.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent ApplicationSer. No. 10/951,208 filed on Sep. 27, 2004 which is a continuation ofU.S. patent application Ser. No. 10/357,502 filed on Feb. 4, 2003, nowU.S. Pat. No. 6,808,506 on Oct. 26, 2004 which claimed priority to thefollowing U.S. Provisional Patent Applications, identified byapplication No. and filing date: No. 60/353,194, filed Feb. 4, 2002; No.60/397,038, filed Jul. 22, 2002; No. 60/407,284, filed Sep. 3, 2002; No.60/420,233, filed Oct. 23, 2002; No. 60/377,649 filed May 6, 2002; andNo. 60/389,881, filed Jun. 20, 2002. This application is also related toU.S. application Ser. No. 10/951,217, filed Sep. 27, 2004, which hasissued as U.S. Pat. No. 7,083,592 on Aug. 1, 2006. The contents of eachof the foregoing documents are incorporated herein by reference in theirentirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a device and a method for delivering orwithdrawing a substance through the skin of an animal, including humans,and in particular to a method and device for withdrawing or delivering asubstance such as a drug, protein or vaccine to a subject. The inventionalso relates to a device for enhancing the penetration of one or moredermal-access members.

2. Related Art

The skin is made up of several layers with the upper composite layerbeing the epithelial layer. The outermost layer of the skin is thestratum corneum that has well known barrier properties to preventmolecules and various substances from entering the body and analytesfrom exiting the body. The stratum corneum is a complex structure ofcompacted keratinized cell remnants having a thickness of about 10-30microns. The stratum corneum forms a waterproof membrane to protect thebody from invasion by various substances and the outward migration ofvarious compounds.

The natural impermeability of the stratum corneum prevents theadministration of most pharmaceutical agents and other substancesthrough the skin. Numerous methods and devices have been proposed toenhance the permeability of the skin and to increase the diffusion ofvarious substances through the skin in order to be utilized by the body.According to some methods and devices, the delivery of substancesthrough the skin is enhanced by either increasing the permeability ofthe skin or increasing the force or energy used to direct the substancethrough the skin.

Other methods of sampling and delivering various substances through theskin include forming micropores or cuts through the stratum corneum.Numerous substances can be effectively administered by piercing thestratum corneum and delivering a substance in or below the stratumcorneum. In a similar manner, some substances can be extracted from thebody through cuts or pores formed in the stratum corneum. The devicesfor piercing the stratum corneum generally include a plurality ofmicroneedles or blades having a length to pierce the stratum corneum.Examples of these devices are disclosed in U.S. Pat. No. 5,879,326 toGodshall et al.; U.S. Pat. No. 6,494,865 to Alchas; U.S. Pat. No.5,997,501 to Gross et al.; U.S. Pat. No. 4,886,499 to Cirelli et al.;U.S. Pat. No. 6,183,434 to Eppstein; U.S. Pat. No. 5,250,023 to Lee etal.; International publication WO 97/48440; U.S. Pat. No. 5,527,288 toGross et al.; and U.S. Pat. No. 3,595,231 to Pistor. Each of theforegoing documents is incorporated herein by reference in theirentirety.

Some of the above-noted devices include micron-sized needles or bladesand can be effective in delivering or sampling substances. However, manyof these needles and blades have a length of a few microns to a fewhundred microns and typically do not penetrate the skin to a uniformdepth. The natural elasticity and resilience of the skin often result inthe skin being deformed by the needles rather than pierced. Therefore,when a microneedle array is pressed against the skin, the outermostneedles penetrate the skin while the innermost needles do not penetratethe skin or only penetrate to a depth less than the outermost needles.

Moreover, conventional devices have problems with overall height andease of use. As a result, the prior methods and devices for the samplingand administering of substances have exhibited limited success.Accordingly, a continuing need exists in the industry for an improveddevice for the sampling and administering of various substances to thebody.

SUMMARY OF THE INVENTION

These and other objects are accomplished by a method and deviceaccording to the present invention.

A device for delivering or withdrawing a substance, typically a fluid,below the stratum corneum is provided. A body of the device includes atop face, a bottom face spaced from the top face, and a side edge.Typically, a channel is defined within the body. The bottom faceincludes a first surface area and a second surface area adjacent to andrecessed from the first surface area. The bottom face further includesat least one raised protrusion disposed on the second surface area. Atleast one dermal-access member is provided in each raised protrusion andis in fluid communication with the channel to deliver or withdraw thesubstance.

Similarly, a method of delivering or withdrawing a substance through atleast one layer of the skin of a subject is provided. The methodincludes the steps of: providing a device having a body having a topface, a bottom face spaced from the top face, and a side edge, the bodydefining a channel within the body, and at least one dermal-accessmember coupled to and extending outwardly from the bottom face and beingin fluid communication with the channel, wherein the bottom faceincludes a first surface area and a second surface area adjacent to andrecessed from the first surface area, the bottom face further includingat least one raised protrusion disposed on the second surface area, atleast one dermal-access member installed in at least one raisedprotrusion; positioning the dermal-access member on a target site of theskin of the subject; applying a pressure against the device sufficientfor at least one dermal-access member to penetrate the skin and for thefirst surface area to contact the skin; and delivering a substance to orwithdrawing a substance from the target side of the subject.

In particular, a method and apparatus for delivering a substance, suchas a drug, protein or vaccine, into or below the stratum corneum of theskin to a sufficient depth where the substance can be absorbed andutilized by the body is provided.

The device and method according to an embodiment of the presentinvention are suitable for use in administering various substances,including pharmaceutical and bioactive agents, to a subject, preferablya mammal, and particularly to a human patient. Such substances havebiological activity and can be delivered through the body membranes andsurfaces, and particularly the skin. Examples include, but are notlimited to antibiotics, antiviral agents, analgesics, anesthetics,anorexics, antiarthritics, antidepressants, antihistamines,anti-inflammatory agents, antineoplastic agents, vaccines, including DNAvaccines, and the like. Additional substances that can be delivered to asubject include proteins, peptides and fragments thereof. The proteinsand peptides can be naturally occurring, synthesized or produced byrecombination.

The device and method may also be used for withdrawing a substance ormonitoring the level of a substance in the body. Examples of substancesthat can be monitored or withdrawn include blood, interstitial fluid orplasma. The withdrawn substances may then be analyzed for variouscomponents or properties.

The dermal-access member according to the invention is any member whichpenetrates the skin of a subject to the desired targeted depth within apredetermined space without passing through it. In most cases, thedevice will penetrate the skin to a depth of about 0.3-3 mm. Generally,the device is utilized for intradermal administration, for example, witha configuration sufficient to penetrate at a depth of about 1.0-1.7 mm.However, the device can also be used to deliver a substance to a depthof about 0.3 mm or less and at subcutaneous depths of 1.7 mm-3.0 mmdepths or greater.

The dermal-access members may comprise conventional injection needles,catheters or microneedles of all known types, employed singularly or inmultiple member arrays. The terms “dermal-access member” and“dermal-access members” as used herein are intended to encompass allsuch needle-like structures. The dermal-access members can includestructures smaller than about 28 gauge, typically about 29-50 gauge whensuch structures are cylindrical in nature. Generally, the dermal accessmembers will be about 30-36 gauge. Non-cylindrical structuresencompassed by the term dermal-access member would therefore be ofcomparable diameter and include pyramidal, rectangular, octagonal,wedged, triangular, hexagonal, cylindrical, tapered and othergeometrical shapes and arrangements. For example, the dermal-accessmembers can be microtubes, lancets and the like. Any suitable deliverymechanism can be provided for delivering the substance to the penetratedskin.

By varying the targeted depth of delivery of substances by thedermal-access members, pharmacokinetic and pharmacodynamic (PK/PD)behavior of the drug or substance can be tailored to the desiredclinical application most appropriate for a particular patient'scondition. The targeted depth of delivery of substances by thedermal-access members may be controlled manually by the practitioner,with or without the assistance of an indicator mechanism to indicatewhen the desired depth is reached. Preferably however, the device hasstructural mechanisms for controlling skin penetration to the desireddepth. This is most typically accomplished by means of a widened area orhub associated with the shaft of the dermal-access member that may takethe form of a backing structure or platform to which the dermal-accessmembers are attached. The length of dermal-access members may be variedduring the fabrication process and can be produced at less than 3 mm inlength. The dermal-access members are typically sharp and of a verysmall gauge, to further reduce pain and other sensation when thedermal-access members are seated in the patient. The invention mayinclude a single-lumen dermal-access member or multiple dermal-accessmembers assembled or fabricated in linear arrays or two- orthree-dimensional arrays to increase the rate of delivery or the amountof substance delivered in a given period of time. Dermal-access membersmay be incorporated into a variety of devices such as holders andhousings that may also serve to limit the depth of penetration. Thedermal-access members of the invention may also incorporate or be influid communication with reservoirs to contain the substance prior todelivery or pumps or other means for delivering the substance into thepatient under pressure. Alternatively, the dermal-access members may belinked externally to such additional components.

The device may include a luer type or other connection port forconnection to a fluid delivery system such as a syringe, a pump, or apen. In such an embodiment, the device may use a length of tubing forfeeding a low dead volume body through an opening in the body.

Any suitable mechanism for delivering a fluid to the dermal-accessmembers can be used. For example, a luer connection can be secureddirectly to the device for delivering a fluid from tubing or directlyfrom a syringe secured to the luer connection. Furthermore, the deviceor portions of the device can be incorporated into an applicator thatapplies the device to a patient in a consistent manner, for example, ata consistent pressure, velocity and dose.

As an option, a removable shield can protect the device andparticularly, the dermal-access members until use.

In addition to being a useful device for penetrating skin at an exactdepth and for supplying an exact amount of fluid, the device is usefulin enabling the placement of multiple dermal-access memberssimultaneously in a patient. This type of application is useful in bothdevice and drug testing applications.

When the device is used to deliver substances to the intradermal spaceof a patient, the delivery of the substance typically results in one ormore blebs left in the skin. As used herein, bleb refers to any site ofdeposition of a substance below the stratum corneum of the skin,generally in the intradermal space. Typically, the bleb extendslaterally from the point of administration and distends upward. The blebdiameter and height are functions of instilled volume and rate ofdelivery and other factors. Secondary physiology effects, such asirritation or histamine release, can also alter bleb dimensions. Blebduration can be a function of uptake distribution and clearance of theinstilled components, both individually and in combination. Multipleblebs can be either overlapping or non-overlapping. Non-overlappingblebs allow for increased area of administration, but may contribute toimbalanced flow to individual points of administration within a system.Overlapping blebs may contribute to increase distension of tissue space,and result in better equilibrium of infusion pressure, but limits thebenefits of increased fluid volume.

The device is constructed for penetrating selected layers of the dermisof a subject to a desired depth. The desired depth of penetration isusually determined by the substance being delivered or withdrawn and thetarget site. In this manner, a substance can be delivered, absorbed andutilized by the body substantially without pain or discomfort to thesubject.

The advantages and other salient features of the invention will becomeapparent from the following detailed description which, taken inconjunction with the annexed drawings, discloses preferred embodimentsof the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The following is a brief description of the drawings.

FIG. 1 is a perspective view of the device in accordance with anembodiment of the invention for sampling or delivering a substancethrough the skin of a subject.

FIG. 2 is an enlarged view of the bottom face of the device shown inFIG. 1.

FIG. 3 is a side elevational view showing the device of FIG. 1interfacing with the skin of a subject.

FIG. 4 is a view of the bleb pattern formed after application of thedevice in FIG. 3.

FIG. 5 is a view of the bottom face of a further embodiment of thedevice.

FIG. 6 is an exploded perspective view of an alternate embodiment of thedevice.

FIG. 7 is a perspective view of the embodiment of the device shown inFIG. 6.

FIG. 8 shows perspective views of the top face and the bottom face ofanother embodiment of the device.

FIG. 9 is an enlarged perspective view of the bottom face of anotherembodiment of the device.

FIG. 10 is a perspective view of the top and bottom faces of anotherembodiment of the device.

FIG. 11 is a perspective view of the top and bottom faces of a furtherembodiment of the device.

FIG. 12 is a perspective view of the top and bottom faces of anadditional embodiment of the device.

FIG. 13 is a perspective view of the device of FIG. 12 with additionalassembled components.

FIG. 14 is a perspective view of the top and bottom faces of a furtherembodiment of the device.

FIG. 15 is a perspective view of the top and bottom faces of a furtherembodiment of the device.

FIG. 16 is a perspective view of another embodiment of the dermal-accessmember array of the device.

FIG. 17 is a table of results for an experiment indicating theeffectiveness of one aspect of the present invention.

FIG. 18A-18D are tables of results for an experiment indicating theeffectiveness of one aspect of the present invention.

FIG. 19 is a table of results for an experiment indicating theeffectiveness of one aspect of the present invention.

DESCRIPTION OF AN EXEMPLARY EMBODIMENT OF THE PRESENT INVENTION

A preferred embodiment of the invention is discussed in detail below.While specific exemplary embodiments are discussed, it should beunderstood that this is done for illustration purposes only. A personskilled in the relevant art will recognize that other components andconfigurations can be used without parting from the spirit and scope ofthe invention.

Referring to the drawings, particularly FIGS. 1 and 2, a first,exemplary embodiment of the invention is now described. As describedherein and shown in all of the figures, analogous or identical featuresare indicated by the same reference number.

A device 10 according to the present invention has a body 12 anddermal-access members 14. The device 10 optionally includes tubing 21for delivering fluid to or removing fluid from the body 12 of thedevice.

The body 12 optionally has a low profile to lie flat against the skin ofa subject. The low profile of the body 12 provides for ease ofattachment to the skin and less obstruction to the subject. The lowprofile can be achieved by reducing the thickness of the body 12. In theembodiment shown, the body 12 has a substantially circular disk shape,although in alternative embodiments, the body 12 can have a non-circularor other more angular shape or be slightly arcuate. As an example, thediameter of the circular body 12 is preferably about 1-10 cm or less,although other sizes and shapes can be used. Embodiments can bemanufactured with diameters of 5 mm or smaller.

The body 12, as shown in FIG. 2, has a circular outer side edge 16, atop face 20 and a bottom face 18. The outer side edge 16 preferably hasa rounded surface. The rounded surface helps control the pressuredistribution on the device 10 and subject during application. Taperingand contouring help tension the skin at a controlled rate to allow thedermal-access members 14 to penetrate the skin with less force thanwould otherwise be required.

One or more fluid channels 22 are provided in the body 12. The fluidchannel 22 has an open inlet end 24. A coupling member 26 is optionallyprovided for coupling a fluid delivery mechanism to the body 12 at theopen inlet end 24. Alternatively, no coupling member is provided and thefluid delivery mechanism is secured directly to the body 12. An axis ofthe fluid channel 22 optionally extends substantially parallel to theplane of the body 12. In this manner, the body 12 maintains asubstantially flat, low profile configuration. Of course, otherarrangements of the coupling member 26 and the fluid channel 22 arepossible.

In the embodiment shown in FIGS. 1 and 2, the bottom face 18 of the body12 has first 28 and second 30 surface areas. The first surface area 28is raised from the body 12 with respect to the second surface area 30.Thus, the second surface area 30 defines a recessed area on the bottomface 18 relative to the first surface area 28.

Raised protrusions 32 are provided in the recessed second surface area30. As an exemplary embodiment, each protrusion 32 can be formed as araised conical protrusion. As an alternative, other shapes such ascylindrical shapes may be used. Optionally, a raised conical protrusion32 can have a flat upper surface to form a conical plateau or lowerfrustum of a cone. As an alternative, other upper surface shapes andcontours may be used.

As shown in FIGS. 1 and 2, the recessed second surface area 30 comprisesa central recessed area 34, preferably located in the center of thebottom face 18, and substantially circular recessed areas 36 surroundingeach of the protrusions 32. In one embodiment, the recessed secondsurface area 30, including the central recess 34 and other recesses 36,are recessed at about 1 mm relative to the surrounding first surfacearea 28, although the depth of the recess can vary from about 0.1 mm andless to about 10 mm. As an example, the recesses 36 surrounding each ofthe protrusions 32 are about 5 mm in diameter, although the diameter ofthe recess can vary, for example to about 50 mm. The recesses 36typically provide an area for the bleb to form. The diameter andarrangement of the recesses 36 and corresponding protrusions 32 candepend on the desired delivery characteristics. Other suitable recessarrangements can be designed depending on the bleb characteristicsdesired, the volume of substance to be delivered, the rate of deliveryof the substance, and other factors. As one option, the diameter of therecess 36 surrounding each of the protrusions 32 can be calculated byone of ordinary skill in the art based on the volume and rate of thefluid administered.

As shown in FIG. 2, the three protrusions 32 and corresponding recessedareas 36 are spaced at 120° relative to one another on the bottom face18, although arrangements can vary. Some of the alternative arrangementare shown in further embodiments and discussed herein. In the embodimentshown, the center of each protrusion 32 is equally spaced at a distanceof about 7.5 mm from the center of the bottom face 18, although, asdiscussed above, other arrangements can be used depending on the desireddelivery characteristics. As an example, the protrusions 32 are about 2mm in diameter at the top of the protrusion 32 and may have anapproximately 10° draft from top to base. The draft of the protrusions32 can range, for example, from 0° to 60°. The shape and sizes of theprotrusions 32 can vary, although typically, the top of the protrusionwill range from 0.5 mm or even smaller to about 10 mm in diameter. Thediameter and shape of the protrusions 32 can be based on, for example,dermal-access member seating requirements.

In the embodiment shown, one dermal-access member 14 is provided in eachconical protrusion 32, although multiple dermal-access members 14 can beprovided in each conical protrusion. Thus, in the embodiment shown inFIGS. 1 and 2, three dermal-access members 14 are provided.

The upper surface of the raised conical protrusion may be slightlyelevated relative to the first surface area 28, flush with the firstsurface area 28, or slightly recessed relative to the first surface area28. It is understood that the relative heights of the respectivesurfaces may vary depending on desired bleb formation, skin tensioningcharacteristics, and dermal-access member seating requirements. As anexemplary embodiment, the first surface area 28 will be slightly lowerthan the top of the protrusions 32, for example 0.25 mm shorter.

Outside of the first surface area 28, the device 10 chamfers to theouter edge 16 to prevent or reduce edge effect, defined as pressureapplied to the outer edge of the device that may impede performance ofthe device 10 or cause the subject discomfort.

In the embodiment shown, each dermal-access member extends about 1 mmfrom the top of the protrusion 32 with about 0.5 mm to about 2 cm of thedermal-access member remaining within the protrusion 32. In an exemplaryembodiment, the device uses hollow dermal-access members 14. Thedermal-access member tips can be beveled, for example, at a single bevelangle of approximately 15-35°, preferably 28°.

As shown in FIG. 2, the fluid channel 22 extends between the inlet 24and the protrusions 32 for supplying a substance to the dermal-accessmembers 14 or for directing a substance withdrawn from a subject to asuitable collection container. In one embodiment, the top face 20 of thebody 12 defines the channel 22. Optionally, the channel 22 is open withrespect to the top face 20. The channel 22 extends from the openinginlet 24 to each of the dermal-access members 14. In the embodimentshown, the channel 22 includes a central channel 23 from the inlet 24 tothe center of the top face 20 and extends from the center outwardly toeach protrusion 32.

The device 10 can also include a cover portion (not shown in FIGS. 1 and2) for covering the channel 22. The cover portion may be glued onto thebody 12 with UV cure adhesive or other attachment mechanism.

In the embodiment shown, the tubing 21 delivers fluid to the channel 22.The tubing 21 is secured to the inlet end 24 of the body 12. The tubing21 may be glued to the coupling member 26. Optionally, the tubing 21includes 16 gauge catheter tubing with a luer fitting. (not shown) Theother end of the tubing can be connected to a supply or receivingdevice. The supply device may be a syringe (not shown), a unit dosedelivery device (not shown), or a suitable metering pump or infusiondevice (not shown) for delivering a substance to device 10 at acontrolled rate. This method can also be used to withdraw a substancefrom a subject.

In an exemplary embodiment, the channel 22 is smaller than the tubing 21feeding the channel 22, but significantly larger than the exit diametersof the dermal-access members 14 so as not to result in unnecessary highpressures. The tubing should not be the limiting factor in the flow ofsubstance through the device. Optionally, the size and configuration ofthe dermal-access member and arrangement of recesses are the primaryfactors in controlling substance delivery. The body 12 of the deliverydevice is preferably designed to deliver fluids in the range of about2-5 psi up to about 200 psi, for example, 50-75 psi. The body 12 canalso be designed to deliver at higher and lower pressures. The body andall fitting and components of the device should be rigid enough towithstand pressures on the device without deflection or loss of liquidsealing.

The device 10 may be taped with tape 38, or otherwise secured, onto asubject during application. Alternatively, the device can be manuallyheld in place without any other securing mechanism. The device 10 canalso be designed and/or manufactured with tape or other suitablesecuring mechanism, such as an adhesive, as part of the device 10.Optionally, the device can be installed or incorporated into anapplicator device for mechanically applying the device to a user.

FIG. 3 illustrates the delivery device of FIGS. 1 and 2 in use, taped tothe subject 40. FIG. 4 shows the bleb pattern resulting from theapplication shown in FIG. 3. As shown in FIG. 4, application of thisembodiment of the delivery device results in a three-bleb pattern.

FIG. 5 shows another embodiment of the device. This embodiment issimilar to the previous embodiment. However, instead of the three memberarray shown in FIGS. 1-3, the device shown in FIG. 5 includes a sixmember array with six protrusions 32 and six dermal-access members 14.

FIG. 6 shows a further embodiment of the device. Other than thedifferences discussed below and illustrated in the Figures, thisembodiment is similar to the other embodiments. This embodiment is asingle member delivery device 10 with one protrusion 32 and onedermal-access member 14. The device 10 shown in FIG. 6 also differs fromthe devices of FIGS. 1-5 in that a flange 44 is provided for applicationof adhesive.

In the example shown in FIG. 6, the body 12 is optionally about 3.8 cmor less in diameter, for example, about 1.2 cm. On the center of thebottom face 18 in the recessed second area 30, the protrusion 32 isformed. In this embodiment, the central recessed area and the circularrecessed area are the same area 30 because only one centrally locatedprotrusion 32 is provided. One dermal-access member is installed in theprotrusion 32.

A chamfer 42 extends to the edge of the device. The chamfer 42 helpsensure that the proper pressure is applied to the dermal-access member14 and prevents any adverse effect of the edge from the device duringdelivery.

In the embodiment shown, the flange 44 surrounds the edge of first area28 for application of an adhesive ring 46. The flange 44 can, forexample, extend about 1 cm beyond the edge of the device. The flange canbe rigid or flexible and can be designed to extend as far as necessarybeyond the edge of the body 12, depending on the necessary level ofsecurement and its placement on the subject. The flange 44 should beslightly recessed relative to the first areas 28 to compensate for thethickness of the adhesive 46, and to minimize or eliminate interferencewith the delivery area. For example, the flange can be recessed 1 mmalthough the amount the flange 44 is recessed can vary. Generally, theadhesive 46 should be located at a distance from the delivery site,preferably, as far away as is practical, so as not to interfere withdelivery characteristics.

The adhesive 46 is preferably a pressure sensitive adhesive capable ofattaching the device 10 to the surface of the skin of a subject and ispreferably applied directly to the flange 44. The adhesive 46 can be adouble-faced adhesive foam tape having one face bonded to the flange 44.The device 10 is preferably packaged with a release sheet covering theadhesive 46 that can be removed immediately before use. As analternative, any suitable means for maintaining biological interface ofthe device with a subject may be used.

The flange 44 and adhesion arrangement 46 can also be provided in theother embodiments.

The top face 20 of the body 12 defines a channel 22 for insertion oftubing 21 for delivery of the fluid. This feature may be present in theother embodiments, although not clearly shown in previous figures. Thechannel 22 may extend from the edge of the main body 12 to the center ofthe top face 20 of the body 12 and is in fluid communication with thedermal-access member 14. In the exemplary embodiment, the tubing extendsinto the body to a narrowing stop in the channel. However, the devicecan be designed with the tubing extending only to the edge of the deviceor all the way through the channel to the dermal-access members. Thechannel 22 can be, for example, about 1 mm in diameter, although thechannel can be modified depending on the desired deliverycharacteristics, including delivery rate and volume. The channel 22 cannarrow as necessary to reduce any dead space inside the device butoutside the tubing. For example, the channel can be, for example, 0.5 mmin diameter or less. Dead space results in wasted substance remaining inthe device and not delivered to the subject and/or requires morepressure than would otherwise be necessary to deliver the substance tothe subject. The top face 20 of the body 12 also has a raised area 52 onthe center of the top face 20. The raised area 52 has a wall or rib 50surrounding the fluid channel 22 to enhance sealing of the channel 22and to prevent any adhesive from wicking into the fluid channel duringassembly. As an example, the rib 50 can be about 0.5 mm in height.

A cover portion 47 is provided to seal the fluid channel 22. The coverportion 47 has an inside face and an outside face (not shown).Preferably, the cover portion 47 is circular with a recess 49 on theinside face that accommodates the raised area (not shown in FIGS. 6 and7) on the top face 20 of the body 12. As an example, the cover portion47 can have a diameter corresponding to the body 12 of the device 10.The recess 49 can be deep enough to accommodate the corresponding raisedarea of the body. The recess 49 and raised area 52 of the body act as alocating aid for placement of the cover portion. The inside of the coverportion 47 can also define a groove (not shown) which mates with the rib50 on the top face 20 of the body 12. Preferably, the groove is moreshallow than the rib 50 to prevent any possible wicking of adhesive. Therib 50 on the top face 20 allows for location and alignment of the coverportion 47. The cover portion 47 and raised area 52 can also be designedto account for adhesive used to adhere the cover portion to the body 12.The cover portion 47 defines a mating half of the fluid channel 22 toallow for obstruction free insertion of the tubing 21. The cover portion47 can be of sufficient thickness to help reduce deflection of the coverportion when pressurized. As an option, the cover portion 47 should notbe set on the flange 44, but instead, on the body, which, as discussedabove, is of a rigid design to prevent deflection.

Shield 48 can be provided for protecting the dermal-access member 14before use. As shown in FIG. 6, the shield 48 can have a tabbed lid withthree slots to allow it to be press fitted inside the diameter of theadhesive ring. Alternatively, the shield 48 can have any suitable designwhich protects the dermal-access member prior to use.

FIG. 7 shows the assembled device from FIG. 6.

FIG. 8 shows another embodiment of the invention in obverse and reverseviews. This embodiment is similar to the embodiment shown in FIG. 6. Thebottom face 18 of the body has a six member array of six protrusions 32and six dermal-access members 14. The bottom face 18 has a raised firstsurface area 28 and a recessed second surface area 30. The protrusions32 are provided on the second surface area 30. The bottom face 18 alsohas a chamfered surface 42 extending from the first surface 28 to theedge 43. A flange 44 is provided for application of adhesive. FIG. 8also shows the top face 20 of the body 12. Fluid channel 22 is shownextending from the inlet port 24 at the edge of the body to the centerof the body 12. The fluid channel 22 also extends from the center of thedevice to each protrusion 32 to deliver fluid to the dermal-accessmembers 14. A cover portion (not shown) can be provided to enclose theopen channel.

FIG. 9 is an enlarged perspective view of the bottom face of anotherembodiment. The bottom face 18 of the body 12 shown in the embodiment ofFIG. 9 is similar to the device shown in FIG. 7. The embodiment of FIG.9 is a single member array with a single protrusion 32. Instead of beinga conical protrusion, the protrusion 32 has arms extending at 120° fromone another. The device of FIG. 9 has a three portion first surface area28 and an edge 16 that chamfers to the flange 44.

As shown by the alternate protrusion shown in FIG. 9, the protrusions ofany of the embodiments can be any suitable shape or arrangement toachieve optimal results. For example, the protrusions can havecylindrical, pyramidal, or other geometrical configurations. As afurther alternative, the protrusions can be arranged as a type of sleevesupporting the dermal-access member which retracts upon application. Theprotrusions can be arranged on a flexible hinge region, such as aflexible membrane or temperature sensitive polymer, which also retractsin a longitudinal direction upon application. In addition, the uppersurface of the protrusion can be flat, concave or convex. Alternatively,the dermal-access member can be supported directly on the second surfacearea without any protrusion or with a protrusion that provides minimalsupport.

FIG. 10 is a perspective view of the top 20 and bottom 18 faces ofanother embodiment of the present invention. The device shown in FIG. 10is a three member array with three protrusions. Instead of having alongitudinal channel defined on the top face of the body, which extendsfrom the edge of the device to a dermal-access member, the embodiment ofFIG. 10 has individual channels 25 in fluid communication with thedermal-access members (not shown in FIG. 10). In the embodiment shown,the individual channels 25 extend perpendicularly directly from the topface 20 to the protrusions 32 and the dermal-access members. Anysuitable mechanism, such as a syringe or pump, can be used to deliver orextract fluid from the individual channels 25. Individual channels 22can be useful in delivering different fluids to a subject or deliveringfluids at different pressures. For example, as shown in FIG. 10, threeseparate delivery means could deliver fluid to the device.

FIG. 11 is a perspective view of the top 20 and bottom faces 18 ofanother embodiment of the present invention. The device shown in FIG. 11is a three point array with three protrusions 32. Instead of having alongitudinal channel defined on the top face of the body which extendsfrom the edge of the device to a dermal-access member, the embodiment ofFIG. 11 has a reservoir 23 defined on the top face 20. Fluid isintroduced from the relatively shorter longitudinal channel into thereservoir 32. The fluid is communicated from the reservoir 23 to thedermal-access member (not shown in FIG. 11).

FIGS. 12-15 show still further embodiments of the device. Generally, theembodiments shown in FIGS. 12-15 are smaller than those shown in FIGS.1-3 and 5-11.

The device 10 shown in FIGS. 12 and 13 is a three member array with abottom face 18 having three protrusions 32 and a flange 44. As shown inFIG. 12, the dermal-access members have not yet been installed. The topface 20 has a raised portion 54 at least in part defining flow paths tothe protrusions and configured to receive a cap assembly 53. The capassembly 53 and tubing 21 for delivering the fluid to the patient duringuse is shown in FIG. 13.

As an example, the device 10 shown in FIGS. 12 and 13 has a thickness ofabout 5 mm and a diameter of about 18 mm with the flange 44. The bodychamfers at 45° to the flange 44. The protrusions 32 extend slightlyabove the raised first surface area 28, for example about 0.2-0.3 mmabove the first surface area 28. The top face of each of the protrusions32 is about 2 mm in diameter. The protrusions 32 are spaced equallyaround the center of the top face 20, and the distance from the centerof a protrusion 32 to the center of the device 10 is 2.5 mm.

The device 10 shown in FIG. 14 is a single dermal-access member devicewith a bottom face 18 having a single dermal-access member installed inthe protrusion 32. The top face 20 has a raised portion 54 at least inpart defining a flow path to the protrusion and configured to receive acap assembly (not shown).

By way of example, the device 10 shown in FIG. 14 is about 5 mm thickand has a diameter of about 18 mm with the flange 44. The protrusion 32extends slightly above the raised first surface area 28, for exampleabout 0.2-0.3 mm above the first surface area 28. The top face of theprotrusion 32 is about 2 mm in diameter.

The device 10 shown in FIG. 15 is a three dermal-access member lineararray with a bottom face 18 having three protrusions 32. The top face 20has a raised portion 54 at least in part defining flow paths to theprotrusions and configured to receive cap assembly (not shown). Thedermal-access members are not yet installed in FIG. 15. Both the device10 and body 12 are elliptical.

By way of example, the elliptical embodiment of the device 10 shown inFIG. 15 is about 5 mm thick and has length of about 19.5 mm and a widthof about 23 mm. The body 12 has a length of about 15 mm and a width ofabout 9 mm. The protrusions 32 extend slightly above the raised firstsurface area 28, for example about 0.2-0.3 mm above the first surfacearea 28. The top faces of the protrusions 32 are about 2 mm in diameter,and the center of a protrusion is spaced about 3 mm from an adjacentprotrusion.

Another embodiment of the dermal-access member array is shown in FIG.16. It includes a linear dermal-access member array with a manifold 33for holding the protrusions 32 and dermal-access members 14 having arectangular face and a generally parallelpiped shape. Typically, theembodiment shown in FIG. 16 is integrated into device 10. Other than theprotrusions, the embodiment of FIG. 16 has a planar face. The face canhave a length of about 4.8 mm, and a width of about 11 mm. Theprotrusions have a linear arrangement and are spaced about 3 mm apartfrom one another. The diameter of the conical protrusions are relativelysmall, for example, about 0.95 mm or smaller.

The arrangement and relative heights of the dermal-access members,recesses, and protrusions can be modified to accomplish or emphasize anynumber of intended beneficial characteristics of the invention.Specifically, the length, width and spacing of the dermal-access memberscan vary depending on the pharmaceutical agent being administered orrequired to penetrate the skin to the optimum depth for the specificpharmaceutical or bioactive agent being administered. The device of thepresent invention maximizes the effective penetration of dermal-accessmembers to a targeted depth. The device can control the size of thebleb. In a device with multiple dermal-access members, the device can beengineered to control the instillation patterning of individual blebsand their relationship to each other. Non-communication betweenindividual dermal-access members can be meaningful for deposition oflarge volumes in a broad biological space or the deposition of multiplefluids, or in designing the pressure parameter of a dermal-accessmember. The device can be designed to provide sufficient fluid flow pathto accommodate the desired velocity and rate of fluid to be instilledand to minimize the amount of void volume. The device can further bedesigned as a function of the desired bleb pattern and for applicationof a particular fluid at a particular site to minimize the area ofapplication.

Generally, the patterning of the dermal-access members can be designedto achieve desired characteristics. Typically, a minimal number ofdermal-access members can be used to reduce the pain or the perceptionof pain by a subject, manufacturing complexity or cost, the number ofpotential failure points, the complexity of the device fluid dynamics,and the dose lost to void volumes in the device or system. The number ofdermal-access members can be increased to decrease the possibility ofblocked fluid paths, to increase the distribution area of instilledfluid to accommodate a greater volume or delivery rate, and topotentially increase uptake.

Alternate arrangements for delivering fluid to the dermal-access membersinclude but are not limited to multiple reservoirs; a manifoldarrangement in which fluid is communicated from a reservoir, throughindividual channels to the dermal-access members; and independentchannels. In addition, the channels can be provided with individual orcombination valving or other means for fluid flow rate control.

As discussed above, the number and arrangement of dermal-access membersand protrusions in each of the embodiments can depend on the desiredrange of fluid delivery volume. Furthermore, the recessed second surfacearea surrounding each protrusion can be arranged based on the desiredrange of fluid delivery volume. For example, a three member array thatdelivers 100 μl of fluid may have recesses surrounding eachdermal-access member of approximately 5 mm in diameter. Conversely, asingle member array that delivers 100 μl of fluid may have a recesssurrounding the single dermal-access member with an approximately 10 mmdiameter. As discussed above, the size and arrangement of the recessesdepend on the desired flow characteristics, including the volume andrate of delivery of the substance.

A method for delivering or withdrawing a substance through the skin isalso provided. The device is positioned in a target site on the surfaceof a subject's skin. The body is pressed downwardly against skin with apressure sufficient to cause dermal-access members to penetrate thelayers of skin. The depth of penetration is dependent upon the length ofdermal-access members, the spacing of the dermal-access members, and thedimensions of the body, including the height of the protrusion, pressureexerted on the device, and the tensioning of the skin resulting from thebody.

The skin of a subject has elastic properties that resist penetration bythe dermal-access members. The skin can be stretched by the raised firstsurface area until the skin is taut before the dermal-access memberspenetrate the skin. A penetrating pressure can be applied to the deviceuntil the first surface area contacts the skin. This promotes uniformpenetration of the skin by each of the dermal-access members.Consequently, when the device is secured to skin with either a manualapplication or adhesive, a pressure is constantly applied todermal-access members 14.

A substance is supplied to the device and fed to dermal-access membersfor delivery to the subject. In alternative embodiments, a substance iswithdrawn from the subject in a similar manner.

For a bolus type injection, the spacing of the delivery points is not asimportant because the pressure is higher and delivery occurs at eachdermal-access member approximately simultaneously. Dermal-access memberspacing in the bolus type injection may determine whether a single blebor multiple blebs form.

For lower rate deliveries, it is beneficial to ensure that the deliverypoints are spaced close enough together to create a single bleb. Asdelivery at a particular dermal-access member in a multi-dermal-accessmember device begins, the pressure at that particular dermal-accessmember decreases. At relatively low delivery pressures, if thedermal-access members are spaced too far apart, the first dermal-accessmember to form a bleb will be the preferential path because thesubstance to be delivered will inherently follow the path of leastresistance. Thus, by having all the points feed the same bleb, nopreferential flow through a particular dermal-access member or deliverypoint should occur because pressure will be equalized across thedermal-access members.

The device of the invention can remain interfaced with the skin forsufficient time to withdraw from or deliver to the subject the desiredsubstances. The length of time the device is required to be attached orin communication with the skin of the subject is usually dependent onthe substance being delivered or withdrawn, the volume of the substance,the target area on the skin, the depth of penetration, and the numberand spacing of dermal-access members. The amount of time the device issecured to the skin may reduce the amount of leakage from the skin afterdelivery of the fluid.

Many of the considerations in designing the device of the presentinvention involve proper placement of the dermal-access members,including placement of the dermal-access members at the proper depth.Specifically, pharmacokinetics (PK) for certain classes of medicamentscan be improved by administering the medicament at a specified placebelow the stratum corneum.

Generally, deposition in intradermal tissue results in faster drug onsetkinetics for system uptake and bioavailability, and increasedbioavailability for some drugs. However, intradermal delivery is limitedin that intradermal tissue space is highly compact and has limitationson the total amount of volume which can be administered, the rate atwhich such fluid can be administered, and the pressure required toadminister such volume. Generally, the subcutaneous layer is not wellperfused by capillaries. As such, absorption is both slower, and in somecases, decreased bioavailability.

Thus, the PK outcome of dermal-access delivery is specific to thedeposition depth and patterning of the administered fluid and suchdeposition can be mechanically controlled via design of the device ofthe present invention. It has been shown that delivery of medicaments totwo different depths increases the PK benefits, for example, delivery toboth shallow subcutaneous areas and intradermal areas.

The present invention can include a device to deliver the medicament totwo different depths, and specifically, to two different physiologicaltissue compartments, such as shallow subcutaneous and intradermal. Thiscan be accomplished, for example, by dermal-access members of differentlengths. Other geometric or mechanical mechanisms can also be designedto deliver fluids to different depths. The device can also be providedwith flow restrictors to deliver differing amounts of fluid to differentareas.

For each of the embodiments discussed herein, the device is optionallyradiation stable to allow for sterilization, if radiation is to be used.Optionally, the body should be transparent or translucent to allow forlight to penetrate and cure the UV adhesive holding the dermal-accessmember secure. As another option, the body can be opaque and epoxy canbe used to secure the dermal-access member. It is noted that having atransparent body enables a user or other person administrating thedevice to properly prime the device by ensuring that no excess air is inthe device. Furthermore, the body and cover portion material should bestiff enough so as not to deflect during normal use conditions andshould be able to withstand internal fluid pressure in the range ofabout 2-5 psi to about 200 psi without failure or leaks. However, theflange and adhesive can be as flexible as necessary for comfortable andsecure attachment to the subject. The body and cover portion materialcan selected to be non-affected by the drug and having no effect on thedrug candidates to be used. The body and the cover portion materialshould also be hypoallergenic.

The device of the invention can optionally be used as a disposable,single-use device. The device can be sterilized and can be stored in asuitable sterile package.

Adequate dermal-access member seating is an important aspect of thepresent invention. Successful dermal-access member seating is defined aspositioning the dermal-access members in the skin such that fluiddelivered through the dermal-access member or dermal-access members doesnot leak out of the skin.

Generally, there are four factors which contribute to a desirabledermal-access member seating: dermal-access member length, dermal-accessmember protrusion geometry, dermal-access member overtravel, and thedermal-access member seating velocity. Overtravel is defined as theextent that the upper face of the protrusion extends beyond the adhesiveor other securing mechanism of the device i.e., the bottommost face ofthe device. The embodiment shown in FIG. 12 has an overtravel of about 1mm, although more or less overtravel amounts can be adequate to ensureproper dermal-access member seating, for example, about 0.5 mm. Ofcourse, it is also important to avoid any obstructions on the body face.

Exemplary embodiments of the geometry of the device in general and ofdermal-access member manifolds have been discussed above.

Experiments have shown that smaller protrusion diameters increase theeffectiveness of dermal-access member seating. It was believed that thehigher local pressure exerted by the smaller surface of the protrusionfor a given force contributes to the beneficial dermal-access memberseating. It is further believed that the smaller surface area of theface of the protrusion has a smaller local effect on the development ofthe bleb.

In one such experiment, a device was applied to a swine test subject todetermine the effectiveness of smaller diameter protrusions as comparedto larger diameter protrusions. The experiment was conducted at aconstant delivery pressure of 15 psi, with a 50 μL air bolus, and withneedles as the dermal-access members. The protrusions are conicalprotrusions with a flat top surface. The dermal-access members extend 1mm above the top surface of the protrusion. Although the surface is flatin this experiment, as noted above, the top surface of the protrusioncan be concave or convex. If the top surface is concave, the length ofthe dermal-access member is measured from the outer rim of the topsurface to the top of the dermal-access member. If the top surface isconvex, the length of the dermal-access member is measured from theuppermost tangent of the surface to the top of the dermal-access member.

In the aforementioned experiment, the smaller diameter protrusions areabout 1 mm (0.0375″) in diameter and the larger diameter protrusions areabout 2 mm (0.075″) in diameter. The experiment also accounted forvarying amounts of overtravel. The results are shown in FIG. 17. Column“over” describes the amount of overtravel in thousandths of an inch.Column “leaker” states whether the trial leaked or not. Column “blebtype” describes the number and particulars, if any. Column “averagerate” describes the average steady-state flow rate calculated in μL/min.The average rate of a trial that leaked is 0. Column “if no leaks” showsthe average rate of the properly seated trials.

As can be seen from FIG. 17, the smaller diameter protrusions providedbetter needle seating. In addition, overtravel was shown to be a factorin needle seating. The experiment suggested that overtravel greatlyprevents leaking.

Interestingly, overtravel did not seem to negatively affect infusionrates. This was somewhat surprising, given the previous experience withoverdriven or overtraveled needles. It has been the conventionalexperience when using 1 mm needles mounted in catheter tubing thatpushing the catheter into the skin significantly affects the pressurerequired to infuse at a given rate in a constant pressure system.However, the amount of overtravel necessary to produce this effect islikely larger than the maximum overtravel of 0.040″ seen in thisexperiment. This suggests an optimal overtravel amount which can bediscerned from further experiments.

It has further been shown that an increased velocity in the applicationof the dermal-access members can increase the effectiveness of theseating.

An applicator for mechanically applying the device to a patient cancontrol the velocity of the dermal-access members. For example, anapplicator such as a Minimed SOF-SERTER™ insertion device or a BDINJECT-EASE™ device can be modified to apply the device to a user at adesired velocity. The device is driven toward the skin by springscontained in the applicator and results in the dermal-access membersseating into the skin of a subject. Among other factors, the strength ofthe springs determines the velocity of the dermal-access members.

Experiments have shown that there is a continuum of velocity rangeswithin which dermal-access member seating improves with velocity, for agiven skin type, manifold mass, and needle sharpness.

Initial seating experiments in Yorkshire pigs utilized a single springrate of about 5 lbf/in. This allowed a 1.7 gram manifold to be propelledat about 6.3 m/s. At this velocity, most 1 mm and 3 mm dermal-accessmembers seated without leaking. However, a large number of manifolds didnot have enough energy to seat the dermal-access members to the requireddepth. Heavier manifold tests, from a drop-center design, had velocitiesof about 3 m/s. At this velocity, most of the 1 mm dermal-access membersleaked. Similarly, most of the 3 mm dermal-access members produced veryshallow blebs. One manifold arrangement uses two springs with springconstants of 3.2 lb/in, and is less massive than other manifolds. Thismanifold arrangement enables a manifold velocity of about 12 m/s orgreater. With this arrangement, nearly 100% of the dermal-access membersseated properly. Accordingly, it has been shown that, for thisarrangement, a velocity of about 6 m/s to 18 m/s is ideal, optionallyabout 6 m/s to about 25 m/s. It is noted, however, that these resultant,calculated velocities were calculated based on energy conservationequations based on known initial forces, and does not account for anyfriction within the applicator or friction of the dermal-access memberspassing through the skin. The actual velocities in this example could bemuch less, for example, 50% less.

One experiment determining dermal-access member velocity utilizes amechanical applicator in which a device with a three dermal-accessmember manifold is loaded. In this experiment, 34 gauge dermal-accessmembers are used. A coil spring is placed on a post of the manifold totension the manifold in the applicator. A luer and line arrangement cansupply fluid to the manifold at a constant pressure. The applicator isplaced on a swine, the applicator is activated to release the spring todrive the manifold with the dermal-access members into the skin, andfluid is delivered to the subject. In this experiment, the manifold isdriven about 5 mm. The following parameters were considered:

Springs Force: None;

Low: 1 lb. initial spring force, 0.5 lb. final force; or

High 2 lb. initial spring force, 1 lb. final force

Device: Center or Side

Adhesive: Full or Missing (safety)

Septum: With or Without

Member Length: 1 mm or 3 mm

The results are shown in FIG. 18. As can be seen, needle seatingincreases with velocity.

The following is a description of a further experiment demonstrating theimportance of dermal-access member velocity. The tests were conducted todetermine the more effective dermal-access member seating arrangementbetween a side push microinfuser and a drop-center infuser. Thedrop-center manifold (“heavy”) weighs about 7.8 grams, and the side pushmanifold weights about 0.4-0.6 g. Therefore, for a given spring orspring set used to drive the manifold, the drop-center design will be atleast 10 times slower in its initial velocity than the side push design.For this experiment, manifolds weighing about 1.7 grams were used as“light” manifolds. The results are shown in FIG. 19. For the 3 mmdermal-access members, the light manifolds had an average flow rate ofabout 3 times than that of the heavy manifolds. This indicates that forthe 3 mm needles, the heavy manifold seated the needles to aconsiderably shallower depth than the light manifold. This is becauseshallower infusions are known to have a higher back pressure than deeperinfusions. The differences shown in the 1 mm dermal-access members wereeven greater, and none of the heavier 1 mm manifolds were successfullyseated.

The lack of obstructions on the face of the device has also been shownto increase effective dermal-access member seating. For example, theexemplary embodiment shown in FIG. 16 has a single surface, i.e.,without the raised or recessed first or second surface areas discussedin previous embodiments. The effectiveness of needle seating for anobstructionless device face was shown in a further experiment. Thedevice of FIG. 16 was incorporated into a mechanical applicator forapplying the device to a subject at a constant pressure, constantvolume, constant dermal-access member length and constant overtravelamount. The leakage rates for these trials were compared to those oftrials using a device identical to that shown in FIG. 16, except thatthe device had walls extending around the periphery of the bottom faceof the device, flush with the walls of the parallepiped shaped and at aheight equal to that of the tops of the protrusions. The device with thewalls leaked more often than the device without walls. It was determinedthat the presence of a wall on the device only hurts infusionreliability. It is believed that the wall limits the amount ofovertravel of the device, and further, prevents the skin in theimmediate proximity of the protrusions from wrapping around theprotrusions. This agrees with the results of the experiment depicted inFIG. 17 and discussed above.

While various embodiments have been chosen to illustrate the invention,it will be appreciated by those skilled in the art that variousadditions and modifications can be made to the invention withoutdeparting from the scope of the invention as defined in the appendedclaims. For example, the body of the device may be made as an integralone-piece unit. In alternative embodiments, the body can be made fromseparately molded sections or pieces and assembled together. The moldedsections can be assembled using an adhesive, by welding, or by the useof mechanical fasteners. Additionally, any number of dermal-accessmembers may be provided on the device.

1. A device for intradermally delivering a substance through at leastone layer of the skin of a subject, the device comprising: asubstantially circular shaped body having a top face, a bottom facespaced from the top face, and a side edge, the body having a channel,wherein the bottom face includes at least one raised conical frustumshaped protrusion disposed on the bottom face having a skin abutmentsurface; at least one dermal-access member being provided in each of theat least one raised conical frustum shaped protrusion and in fluidcommunication with the channel, wherein the at least one dermal-accessmember extends from about 0.3 mm to about 3 mm from the skin abutmentsurface; a fitting wherein the fitting is operatively and fluidicallycoupled to a fluid delivery system selected from the group consisting ofsyringe, pump, and medication delivery pen; and a tubing having a lumenand a first end and second end, wherein the first end is attached to thetop face of the body, wherein the lumen of the tubing in fluidcommunication with the channel, and the second end of the tubing isconnected to the fitting, and the lumen of the tubing is in fluidcommunication with the fitting.
 2. The device of claim 1, wherein the atleast one raised protrusion conical frustum shaped includes an oddnumber of raised conical frustum shaped protrusions.
 3. The device ofclaim 1, wherein the at least one raised conical frustum shapedprotrusion includes an even number of raised conical frustum shapedprotrusions.
 4. The device of claim 1, wherein the dermal-access memberis a needle.
 5. The device of claim 4, wherein the dermal-access memberis a microneedle.
 6. The device of claim 5, wherein the microneedle is a34, 35, or 36 gauge needle.
 7. The device of claim 5, wherein themicroneedle is smaller than 34 gauge.
 8. The device of claim 5, whereinthe tip of the microneedle has approximately a 28° bevel.
 9. The deviceof claim 5, wherein the channel, the lumen, and the fitting are adaptedto withstand fluid pressures of up to about 200 psi.
 10. The device ofclaim 1, further comprising a flange surrounding at least a portion ofthe body and extending outwardly from the side edge of the body.
 11. Thedevice of claim 1, further comprising a needle shield constructed andarranged to protect the at least one dermal-access member.
 12. Thedevice of claim 1, wherein the fitting further comprises a luer fitting.13. The device of claim 1, wherein the skin abutment surface of the atleast one raised conical frustum shaped protrusion is a generally flatsurface having a diameter of less than 2 mm.
 14. The device of claim 1,wherein the skin abutment surface of the at least one raised conicalfrustum shaped protrusion is a generally flat surface having a diameterof about 1 mm.
 15. The device of claim 4, wherein the needle extendsabout 1 mm from the skin abutment surface.
 16. The device of claim 1,wherein the body is constructed a substantially clear material.
 17. Amethod of delivering a substance through at least one layer of the skinof a subject, the method comprising the steps of: providing a devicehaving a substantially circular shaped body having a top face, a bottomface spaced from the top face, and a side edge having a flange, the bodyhaving a channel, wherein the bottom face includes at least one raisedconical frustum shaped protrusion disposed on the bottom face having askin abutment surface; at least one dermal-access member being providedin each of the at least one raised conical frustum shaped protrusion andin fluid communication with the channel, wherein the at least onedermal-access member extends from about 0.3 mm to about 3 mm from theskin abutment surface wherein the channel is fluidically coupled to afluid delivery system selected from the group consisting of syringe,pump, and medication delivery pen; positioning the at least onedermal-access member on a target site of the skin of the subject;applying a pressure against the device sufficient for the at least onedermal-access member to penetrate the skin and for the skin abutmentsurface to contact the skin; and delivering a substance to the targetsite of the subject.
 18. The method of claim 17, further comprisingadhesively attaching the device to the skin of the subject.
 19. Themethod of claim 17, wherein the dermal-access member penetrates the skinat a targeted depth.
 20. The method of claim 17, wherein the substanceis delivered to an intradermal layer of the skin.
 21. A device forintradermally delivering a substance from a fluid delivery systemthrough at least one layer of the skin of a subject, the devicecomprising: a body having a top face, a bottom face spaced from the topface, and a side edge, the body defining a channel and the body beingadapted to be disposed proximate to the subject's skin; a flangeextending outwardly from the side edge of the body and adapted to begrasped by a caregiver; a raised protrusion disposed on the bottom face,wherein the raised protrusion has a conical frustum shape that defines askin abutment surface; a needle extending from the body a fixeddistance, wherein the needle is disposed proximate to but at a selecteddistance from the skin abutment surface of the raised protrusion,wherein the needle has an inner diameter that is in fluid communicationwith the channel and wherein the needle extends between about 1.0 mm toabout 1.7 mm beyond the skin abutment surface; a fitting is adapted tobe operatively and fluidically coupled to the fluid delivery system; anda flexible tubing defining a lumen and having a first end and secondend, wherein the first end is engaged to the body such that the lumen ofthe tubing is in fluid communication with the channel, and the secondend of the tubing is connected to the fitting such that the lumen is influid communication with the fitting, wherein the tubing has a largerinternal diameter than the needles.
 22. The device of claim 21 whereinthe raised protrusion comprises three protrusions, each having conicalfrustum shapes and being disposed at 120° with respect to each other.23. The device of claim 21 wherein the raised protrusion comprises threeprotrusions, each having conical frustum shapes and being disposed in alinear array.
 24. The device of claim 21, wherein the needle is a 34,35, or 36 gauge needle.
 25. The device of claim 21, wherein the needleis smaller than 34 gauge.
 26. The device of claim 21, wherein the tip ofthe needle has approximately a 28° bevel.
 27. The device of claim 21,wherein the channel, the lumen, and the fitting are adapted to withstandfluid pressures of up to about 200 psi.
 28. The device of claim 21,further comprising a needle shield constructed and arranged to protectthe needle.
 29. The device of claim 21, wherein the fitting furthercomprises a luer fitting.
 30. The device of claim 21, wherein the skinabutment surface of the at least one raised conical frustum shapedprotrusion is a generally flat surface having a diameter of less than 2mm.
 31. The device of claim 21, wherein the skin abutment surface of theat least one raised conical frustum shaped protrusion is a generallyflat surface having a diameter of about 1 mm.